College of Traditional Chinese Medicine, Jinan University, Guangzhou, China.
College of Pharmacy, Jinan University, Guangzhou, China.
J Cell Physiol. 2019 Dec;234(12):23475-23484. doi: 10.1002/jcp.28916. Epub 2019 Jun 12.
MicroRNAs (miRNAs) regulate activities in living organisms through various signaling pathways and play important roles in the development and progression of osteoporosis. The balance between osteogenic and adipogenic differentiation of rBMSCs is closely related to the occurrence of osteoporosis. ERα regulates bone metabolism in various tissues. However, the correlation among ERα, miRNAs, and the differentiation of rBMSCs is still unclear. In this study, we used lentivirus transfection into rBMSCs to construct an ERα-deficient model, analyzed the differences in expressed miRNAs between control and ERα-deficient rBMSCs. The results revealed that the expression of 25 miRNAs were upregulated, 164 miRNAs were downregulated, and some of the regulated miRNAs such as miR-210-3p and miR-214-3p were related to osteogenic or adipogenic differentiation, as well as to particular signaling pathways. Next, we overexpressed miR-210-3p to evaluate its effects on the osteogenic and adipogenic differentiation of rBMSCs, and identified the relationship among miR-210-3p, Wnt signaling pathway, and the differentiation of rBMSCs. The results indicated that ERα-deficient inhibited osteogenic differentiation, promoted adipogenic differentiation, and regulated the expression of some miRNAs. Meanwhile, overexpression of miR-210-3p promoted osteogenic differentiation and inhibited adipogenic differentiation of rBMSCs, processes likely to be related to the Wnt signaling pathway. In conclusion, we identified a group of upregulated and downregulated miRNAs in ERα-deficient rBMSCs that might play a vital role in regulating osteogenic or adipogenic differentiation. One of these, miR-210-3p, inhibited osteogenic differentiation and promoted adipogenic differentiation correlated with the Wnt signaling pathway in ERα-deficient rBMSCs, providing new insight into the regulation of bone metabolism.
微小 RNA(miRNAs)通过各种信号通路调节生物体内的活动,在骨质疏松症的发生和发展中发挥着重要作用。rBMSCs 成骨和成脂分化的平衡与骨质疏松症的发生密切相关。ERα 在各种组织中调节骨代谢。然而,ERα、miRNAs 和 rBMSCs 分化之间的相关性尚不清楚。在这项研究中,我们使用慢病毒转染 rBMSCs 构建了 ERα 缺陷模型,分析了对照和 ERα 缺陷 rBMSCs 之间表达差异的 miRNAs。结果表明,25 个 miRNA 的表达上调,164 个 miRNA 的表达下调,一些调节后的 miRNA,如 miR-210-3p 和 miR-214-3p,与成骨或成脂分化以及特定的信号通路有关。接下来,我们过表达 miR-210-3p 来评估其对 rBMSCs 成骨和成脂分化的影响,并确定 miR-210-3p、Wnt 信号通路和 rBMSCs 分化之间的关系。结果表明,ERα 缺陷抑制成骨分化,促进成脂分化,并调节某些 miRNA 的表达。同时,miR-210-3p 的过表达促进 rBMSCs 的成骨分化,抑制 rBMSCs 的成脂分化,这些过程可能与 Wnt 信号通路有关。总之,我们鉴定了 ERα 缺陷 rBMSCs 中一组上调和下调的 miRNA,这些 miRNA 可能在调节成骨或成脂分化中发挥重要作用。其中之一,miR-210-3p,与 ERα 缺陷 rBMSCs 中的 Wnt 信号通路相关,抑制成骨分化,促进成脂分化,为骨代谢的调节提供了新的见解。